Evaluation of Mepolizumab and Dupilumab Discontinuation in Achieving Sustained Remission in Severe Chronic Rhinosinusitis with Nasal Polyps: A Danish RCT

The primary objective of this study is to evaluate whether patients with severe **Chronic rhinosinusitis with nasal polyps** who have been treated with a monoclonal antibody, specifically **mepolizumab** or **dupilumab**, can discontinue treatment after at least 12 months without symptoms, without experiencing a recurrence of symptoms. This is clinically relevant as it may allow for the reduction of long-term medication use and associated costs, while maintaining patient quality of life.

Secondary objectives include determining if one of the two drugs, mepolizumab or dupilumab, is superior in achieving complete remission. This could provide insights into optimizing treatment strategies for better patient outcomes.

The clinical trial involves participants diagnosed with **chronic rhinosinusitis with nasal polyps**. The study population includes both male and female subjects, aged between 18 and 64 years. Participants are required to be in good general health, without any significant vulnerabilities. The trial population was selected based on specific criteria, including ongoing treatment with either Dupilumab or Mepolizumab, with a stable regimen for at least three months. Participants must have consistently assessed their condition as controlled and maintained a low symptom score over the past year. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified, but participants must not have undergone recent sinus surgery or required rescue treatment for their condition. The ability to understand Danish and provide informed consent is also necessary for inclusion in the study.

The clinical trial is designed to evaluate the discontinuation of **mepolizumab** or **dupilumab** in patients with severe **chronic rhinosinusitis with nasal polyps** who have been symptom-free for at least 12 months. This is a randomized, double-blind, controlled trial with an estimated duration extending until December 2027. The trial will involve participants who are currently receiving either **Nucala 100 mg** or **Dupixent 300 mg** via subcutaneous injection every four weeks. The primary objective is to determine the percentage of patients who can cease biologic treatment while maintaining complete remission. Secondary objectives include assessing any differences in outcomes based on the specific drug used.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, current treatment stability, and symptom control. Follow-up visits will be scheduled at regular intervals to monitor the participants' health status and response to treatment discontinuation. The end-of-study visit will conclude the trial, assessing the long-term effects of treatment cessation. The expected length of participant involvement is up to 52 weeks, with conditions for early termination including significant symptom recurrence or adverse events.

Inclusion criteria require participants to have previously met the EPOS criteria for biologic treatment initiation, including the presence of bilateral polyps and a history of sinus surgery. Participants must also demonstrate controlled symptoms and a low nasal endoscopy polyp score over the past year. Exclusion criteria are not specified, but participants must be able to understand Danish and provide informed consent. The trial is categorized as a phase IV, low-intervention study, as both drugs are approved and used according to recommendations, with the primary investigation focusing on the feasibility of discontinuing treatment.

The clinical trial involves the administration of two experimental medications, **Nucala** and **Dupixent**, both of which are utilized in the treatment of severe chronic rhinosinusitis with polyps. **Nucala** (mepolizumab) is provided as a 100 mg powder for solution for injection. It is administered via **subcutaneous injection**. The maximum daily dose is 100 mg, with a total dose of 1 injection per administration. The treatment period for Nucala is up to 52 weeks. Mepolizumab is a monoclonal antibody, classified under the ATC code R03DX09, and is produced by GlaxoSmithKline Trading Services Limited.

**Dupixent** (dupilumab) is supplied as a 300 mg solution for injection in a pre-filled syringe. Similar to Nucala, it is administered through **subcutaneous injection**. The maximum daily dose for Dupixent is 300 mg, with a total dose of 1 injection per administration. The treatment duration is also up to 52 weeks. Dupilumab is a monoclonal antibody, categorized under the ATC code D11AH05, and is manufactured by Sanofi Winthrop Industrie.

Both medications are not pediatric formulations and are not classified as orphan drugs. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The primary objective of the trial is to evaluate the possibility of discontinuing these treatments after at least 12 months without symptoms, without recurrence of symptoms in patients.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the percentage of patients who can discontinue biologic treatment and remain in complete remission from severe **Chronic rhinosinusitis with polyps** (CRSwNP). The secondary endpoint will explore any differences in outcomes based on the specific biologic drug used, either Mepolizumab or Dupilumab. The trial will involve patients who have been on stable treatment with these biologics for at least three months and have maintained controlled symptoms over the past year.

Data collection will include patient-reported outcomes and clinical assessments to determine remission status. The trial will utilize a Visual Analogue Scale (VAS) to measure symptom severity, ensuring that patients have consistently scored their symptoms at five or below on a scale from 0 to 10 over the past year. Additionally, nasal endoscopy results will be reviewed to confirm a polyp score of no more than 1+1 out of 4+4, with no thick secretions or general edema present. These assessments will be conducted at specified intervals throughout the trial to monitor efficacy and ensure accurate data collection for analysis.